Macrophage CD14 expression in human carotid plaques is associated with complicated lesions, correlates with thrombosis, and is reduced by angiotensin receptor blocker treatment

•The lipopolysaccharide receptor CD14 is expressed in thrombotic carotid lesions.•Angiotensin receptor blocker suppressed expression of CD14 in carotid lesions.•CD14 expression was inhibited by angiotensin receptor blockade in macrophages.•Angiotensin receptor blockade has anti-inflammatory effects.

CD14 is a predictor of inflammation and associated with atherosclerosis. We analyzed 118 carotid plaques from patients with symptomatic carotid artery stenosis for expression of the macrophage markers CD14, CD68 and the angiotensin II type 1 receptor (AT1-R). CD14 staining was significantly increased in thrombotic carotid plaques. AT1-R staining was found in macrophage-rich areas, and AT1-R mRNA was detected in plaque macrophages isolated with anti-CD14 immunobeads. In patients treated with an angiotensin receptor blocker, expression of CD14 and CD68 in carotid plaque and serum levels of inflammatory markers were lower than in untreated patients. In vitro, expression of CD14 in human monocyte-derived macrophages was increased by exposure to lipopolysaccharide and decreased by exposure to an angiotensin receptor blocker. Thus, inhibition of the innate immune responsive lipopolysaccharide receptor CD14 in macrophages, rather than AT1-R inhibition, may help explain the anti-inflammatory effects of angiotensin receptor blockade.